Interplay between autophagy and apoptosis in pancreatic tumors in response to gemcitabine

PAPADEMETRIO D,; CAVALIERE V.; SIMUNOVICH T; COSTANTINO S.; CAMPOS M D; LOMBARDO T.,; FADER KAISER C; ALVAREZ E.

TARGETED ONCOLOGY

SPRINGER

Lugar: Berlin; Año: 2014 vol. 9 p. 123 - 134

1776-2596

Pancreatic cancer is an aggressive disease. Its incidence has increased over the last two decades. It is currently the fourth cause of death among cancers in the western world. Unfortunately, systemic chemotherapy sti l l rel ies on just a few drugs which unti l now have produced unsatisfactory resul ts. Gemci tabine (2′-2′ -di fluorodeoxycytidine) is currently the standard chemotherapy treatment at al l stages of pancreatic adenocarcinoma. Survival benefi t and cl inical impact however remain moderate due to a high degree of intrinsic and acquired resistance. Autophagy plays an important role in cel l death decision but can also protect cel ls from various apoptotic stimul i . We investigated the function of autophagy in pancreatic carcinoma cel ls, which are frequently insensi tive to standard chemotherapeutic agents. Here, we demonstrate that autophagy is one of the mechanisms responsible for the refractory response of pancreatic tumors to gemci tabine. We present evidence in vi tro and in vivo that proves autophagy plays a protective role in pancreatic ductal carcinoma cel ls, preventing them from entering the apoptotic pathway after stimulus wi th gemci tabine, thus contributing to treatment resistance. A better understanding of the role in the process may help in the discovery of new strategies to overcome tumor drug resistance in this aggressive disease